Multiple sclerosis (MS) is a T-cell mediated autoimmune disease of the central nervous system (CNS). Much research related to the immunological aspects of MS has focused on defining the nature of the antigen(s) against which the immune response is generated and the molecule(s) responsible for presentation of these antigens. For many years, the dogma has been that T-cells recognize peptide antigens presented in the context of M11C molecules and substantial research has defined peptide antigens that may contribute to the pathogenesis of MS. Recently, it hasbeen shown that molecules of the CD1 family can act as restriction elements in lipid antigen presentations to specialized subsets of T-cells suggesting that the spectrum of antigens to which T-cells respond may be broader than previously thought. Studies on the identification of these antigens have thus far been directed only to bacterial components. CD1 glycoproteins are cell surface molecules, noncovalently linked to beta2-microglobulin and structurally related to major histocompatibility (M11C) antigens. The CD I family includes CD I a, b and c proteins, products of separate genes that all map to chromosome 1, having molecular masses of 49, 45, and 43 kDa respectively. They are found on all cortical thymocytes, but not on circulating T-cells or monocytes, and are differentially expressed by subpopulations of dendritic cells, Langerhans cells (CDI a and CD I c), subsets of B-cells (CD I c), certain T-cell leukemias, and tissue macrophages in some inflammatory lesions. In the brain, CD I a has been reported on microglia by some investigators, but not others. Battistini et al.. have shown that CDlb, is expressed in active MS lesions. Since lipids, particularly glycolipids, are a major component of the myelin membrane it is reasonable to consider that lipids may be involved in the immunopathology of MS. The immune response would include CD1 molecules presenting lipid antigens to specialized populations of T-cells. To test this hypothesis, the first step is to isolate and characterize a purified lipid antigen that elicits a T-cell response. Recent work has suggested that the glycolipids that elicit the most response contain unusual fatty acids and long chain bases. Therefore, it is important to find if unusual fatty acids or long chain bases are expressed in MS tissues.